PEG-IFN/Ribavirin Experienced, Genotype 3 Patients Without Cirrhosis

Recommended Regimens by evidence level and alphabetically for:

Genotype 3, PEG-IFN/Ribavirin Treatment-experienced Patients, Without Cirrhosis

Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
* The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.
RAS testing for Y93H is recommended for cirrhotic patients and ribavirin should be included in regimen if present.

Daclatasvir plus sofosbuvir

In the ALLY-3 study, treatment-experienced patients without cirrhosis did well with an SVR12 rate of 94% (32/34) (Nelson, 2015).


The phase III ASTRAL-3 study evaluated the fixed-dose combination of sofosbuvir/velpatasvir for 12 weeks without ribavirin in 277 genotype 3-infected patients, including 71 with prior treatment experience and 80 with cirrhosis (Foster, 2015a). Despite a high combined SVR12 rate of 95% (264/277), both prior treatment (90% SVR) and cirrhosis (91% SVR) had a moderate negative impact on treatment responses. The addition of ribavirin did appear to increase SVR12 rates in a phase II study of treatment-experienced genotype 3 patients treated for 12 weeks with 25 or 100 mg of velpatasvir combined with sofosbuvir (Pianko, 2015).

Baseline NS5A substitutions in genotype 3 also impact DAA treatment response, with the Y93H substitution being the most challenging. In the ALLY-3 study the Y93H was detected in 13 (9%) of patients with an SVR12 of 54% (7/13); including a 67% SVR12 in patients without cirrhosis. In the ASTRAL-3 study the Y93H was detected in 25 (9%) of patients with an SVR12 rate of 84% (21/25). Given that cirrhotic patients in whom prior treatment with PEG-IFN/ribavirin has failed are already recommended to have ribavirin added with or without extension of therapy depending on the specific regimen, baseline testing for NS5A RASs in genotype 3 would only impact treatment approaches for patients in whom prior treatment with PEG-IFN/ribavirin has failed without cirrhosis. Pending additional data, baseline NS5A RAS testing is recommended in all treatment-experienced genotype 3 patients without cirrhosis. If the Y93H substitution is identified, weight-based ribavirin should be added to the treatment course.

Last update: 
April 12, 2017

Additional Reading:    HIV/HCV Coinfection    Renal Impairment    Acute Infection